The present invention relates to a process for the selective transesterification of stanols in mixtures comprising sterols and stanols and a process for separating sterols from mixtures containing sterols and stanols.
Steroids, either from plants (phytosteroids) or animals (zoosteroids) are chemical compounds whose molecules present a perhydrocyclopentanophenantrene nucleus and some of them also have a hydrocarbon chain joined to carbon 17 of this nucleus.
Among steroids are the steroid alcohols which present at least one hydroxile group joined to carbon C-3 of the nucleus. In the present invention, the term “sterol” stands for a steroid alcohol comprising a double bond in carbon C-5 of the nucleus. Likewise the term “stanol” stands for a steroid alcohol lacking a double bond in carbon C-5 of the nucleus. Sterols and stanols commonly known in the state of art are included among sterols or stanols of the present invention.
Significant amounts of steroid alcohols can be found in the residue of the degumming of edible oils such as soy bean oil, sunflower oil, maize germ oil, palm oil, rapeseed oil or in the so called wood alcohols derived from black liquor soaps from Kraft cellulose pulping process, or from tall oil, or from the residue of tall oil distillation known as tall oil pitch.
Most steroid alcohols from plants, or phytosterols, which include wood alcohols as well, usually contain both sterols and stanols.
Processes for the recovery and purification of phytosterols are well known in the art. Table I below shows a typical composition of wood alcohols from black liquor soaps.
TABLE ITypical composition of wood alcohols from black liquor soaps.Steroid alcoholPercentage in weightBeta-sitosterol68Beta-sitostanol20Campesterol7Campestanol2Stigmasterol<1
Mixtures of steroid alcohols ocasionally contain steryl or stanyl esters besides free steroid alcohols. To utilize the process of separation herein disclosed in these cases, the mixtures have to be first hydrolyzed, either by enzymatic hydrolysis or alkaline saponification, and the resulting unsaponifiable material comprising sterols and stanols once recovered from the hydrolized or saponified mixture, may be subjected to the fractionation process of the present invention. The process herein disclosed can be used with mixtures of steroid alcohols of either plant or animal origin and also with any unsaponifiable mixture comprising sterols and stanols.
Both sterols and stanols have important commercial applications. Sterols, mainly beta-sitosterol, can be transformed by fermentation into useful intermediaries for the synthesis of steroid drugs. Stanols are less suitable for microbial transformation, therefore it might be advisable to remove them from the mixture of steroid alcohols prior to fermentation. On the other hand, stanols esterified with organic acids, in general fatty acids, or stanyl esters of fatty acids, are efficient blod cholesterol lowering agents and as such are in high demand as nutraceutical ingredients for food products.
Therefore it might be convenient to separate sterols from stanols in mixtures comprising steroid alcohols, in order to obtain pure sterols for the pharmaceutical industry and stanyl esters or stanols for neutraceutical industry. However, no processes for the separation of sterols from stanols are known. Therefore, the pharmaceutical industry has to resort to steroid alcohol mixtures whose fermentation, as explained above is less effcient as that of pure sterols, and the nutraceutical industry for the obtention of stanols or stanol esters has to resort to the transformation of the whole mixture of steroid alcohols into steroid esters. One of such processes is dislosed in U.S. Pat. No. 5,502,045. The process disclosed consists in the catalytic hydrogenation of the mixture of steroid alcohols to reduce sterols to stanols, followed by the chemical transesterification of the mixture using methyl esters of fatty acids in the presence of the catalyst sodium ethylate. Among its disadvantages, hydogenation eliminates the valuable beta-sitosterol, and additionally, the process may lead to the formation of an asymmetric carbon center in C-5, so that enantiomeric mixtures with non-natural configuration isomers and unknown metabolic effects could be generated.
Therefore, it is convenient to separate sterols and stanols from mixtures of steroid alcohols in order to obtain high quality sterols for fermentation or other uses and natural stanols or stanol esters as nutraceutical food ingredients.
However, beta-sitostanol and beta-sitosterol, whose structures are shown below, have practically identical physical and chemical properties turning almost unthinkable any effective technique to separate them. This fact is reflected in the total absence of any reference on the subject in the art.
